dysbiosis
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Dysbiosis (also called dysbacteriosis) is characterized by a disruption to the
microbiome A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably wel ...
resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the
skin flora Skin flora, also called skin microbiota, refers to microbiota (community (ecology), communities of microorganisms) that reside on the skin, typically human skin. Many of them are bacterium, bacteria of which there are around 1,000 species upon hu ...
,
gut flora Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the g ...
, or vaginal flora, can become deranged (unbalanced), when normally dominating
species A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...
become underrepresented and species that normally are outcompeted or contained increase to fill the void. Similar to the human gut microbiome, diverse microbes colonize the plant rhizosphere, and dysbiosis in the rhizosphere, can negatively impact plant health. Dysbiosis is most commonly reported as a condition in the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
or plant rhizosphere. Typical microbial colonies found on or in the body are benign or beneficial. These appropriately sized microbial colonies carry out a series of helpful and necessary functions, such as aiding in
digestion Digestion is the breakdown of large insoluble food compounds into small water-soluble components so that they can be absorbed into the blood plasma. In certain organisms, these smaller substances are absorbed through the small intestine into th ...
. They also help protect the body from infiltration by pathogenic microbes. These beneficial microbial colonies compete with each other for space and resources. However, when this balance is disturbed, these colonies exhibit a decreased ability to check each other's growth, which can then lead to overgrowth of one or more of the disturbed colonies which may further damage some of the other smaller beneficial ones in a vicious cycle. As more beneficial colonies are damaged, making the imbalance more pronounced, more overgrowth issues occur because the damaged colonies are less able to check the growth of the overgrowing ones. If this goes unchecked long enough, a pervasive and chronic imbalance between colonies will set in, which ultimately minimizes the beneficial nature of these colonies as a whole.


Potential causes of dysbiosis

Any disruption of the body’s microbiota is able to lead to dysbiosis. Dysbiosis in the gut happens when the bacteria in the gastrointestinal tract become unbalanced. There are many causes for dysbiosis in the gut. Some reasons include, but are not limited to:   * Dietary changes *
Antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s that affect the
gut flora Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the g ...
* Psychological and physical stress (weakens immune system) * Use of
radiation In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or a material medium. This includes: * ''electromagnetic radiation'' consisting of photons, such as radio waves, microwaves, infr ...
,
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
,
antiviral drug Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials ...
s, radioactive isotopes, and
hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...
* Presence of intestinal helminths ( human parasites) * Uncontrolled rectal cleansing with enemas * Inflammatory process in the intestine * Chronic and acute infections (HIV, Hepatitis C & B, herpes, etc.)


Gut/intestinal dysbiosis

Bacteria in the human gut’s intestines are the most diverse in the human body and play a vital role in human health. In the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...
, dysbiosis manifests particularly during small intestinal bacterial overgrowth (SIBO), commonly caused by a decrease in the passage of food and waste through the gastrointestinal tract following surgery or other pre-existing conditions. SIBO is characterized by symptoms of abdominal pain, diarrhea, discomfort after eating, and malnutrition. Similarly, dysbiosis manifests during small intestinal fungal overgrowth (SIFO) caused by excessive population levels of fungi in a bowel. SIFO can be characterized by GI symptoms (vomiting, diarrhea) in those previously immunocompromised. The consumer’s dietary habits can be one of the most influential factors on the gut’s microbiota. Diets high in carbohydrates and refined sugars are common links to dysbiosis in the gut, whereas those rich in fruits, vegetables, and fish oils are considered more favorable to the gut due to their anti-inflammatory properties. Many diseases, such as IBD, Type 2 Diabetes, Crohn's, and even allergies, are suggested to be due, in part, to an alteration in the microbiome of the gut. Probiotics can sometimes cause mild gas and bloating in people who first start taking them, especially at high doses, as their body gets used to having new gut bacteria introduced into their gut.


Oral dysbiosis

The mouth is frequently exposed to novel microbes from the environment, and this can lead to microbial disturbances in the mouth as well as in the stomach and intestines. Hygiene and nutritional variation are imperative in preventing oral diseases such as gingivitis, tooth decay, and cavities, which are linked to altered microbial communities in the oral cavity. Oral pathogens can affect multiple microbiota compartments of the body and alter systemic processes, such as immunological alterations or digestion issues. Smoking, drinking, oral intercourse, and advanced age are all associated with oral dysbiosis.


Skin dysbiosis

There are a number of types of microorganisms that reside in and on the human skin, collectively known as the
skin flora Skin flora, also called skin microbiota, refers to microbiota (community (ecology), communities of microorganisms) that reside on the skin, typically human skin. Many of them are bacterium, bacteria of which there are around 1,000 species upon hu ...
. Normal healthy microbial communities may have some positive effects. Altered microbial composition and diversity (dysbiosis), may play a role in some non-infectious skin conditions such as
acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...
,
atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin. Atopic dermatitis is also often called simply eczema but the same term is also used to refer to dermatitis, the larger group of skin conditi ...
,
psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...
, and rosacea. In more extreme cases, such as
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
, a pathogenic bacteria can infect the skin, the most common being Streptococci species and
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
.


Vaginal dysbiosis

The vagina contains a microbiome ( vaginal flora) that can become disturbed and result in conditions such as
bacterial vaginosis Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urina ...
. Alterations in vaginal flora can also affect vaginal health in reproduction, as well as one's risk of acquiring and the subsequent severity of sexually transmitted infections.


Role of antibiotics in promoting dysbiosis

Dysbiosis can occur during many stages of life and can be triggered by many different sources. Antibiotics, for example, are often a significant contributor to disruptions in microbiomes. This occurs because not all microbes will be affected by the antibiotic in the same way, and so it can change the balance of different types of microbes as well as changing the total number of microbes. Antibiotic usage during young childhood development can lead to adverse gut issues (dysbiosis) in adulthood. The gut microbiome is altered from antibiotics and is linked to future gut disease, i.e., IBD,
ulcerative colitis Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...
, obesity, etc. The intestinal immune system is directly influenced by the gut microbiome and can be hard to recover if damaged through antibiotics. The use of minocycline in acne vulgaris has been associated with skin and gut dysbiosis.


Effects

Gut dysbiosis has been linked to the pathogenesis of both intestinal and extra-intestinal disorders. Dysbiosis may affect intestinal disorders include IBD, IBS, and coeliac disease, as well as extra-intestinal conditions including allergies, asthma, metabolic syndrome, cardiovascular disease, and obesity. Gut dysbiosis can also be a factor in neurodegenerative and cerebrovascular diseases due to the link between age-related dysbiosis and inflammation. Inflammation is a common factor for a wide variety of age-related pathologies, including neurological diseases. By correcting the dysbiosis in elderly patients, it may be possible to prevent the development of neurodegenerative diseases. Dysbiosis may contribute to the cause or development of neurological conditions, including autism, pain, depression, anxiety, and stroke. Dysbiosis contributing to neurological conditions is due to interactions with the gut-brain axis allowing the gut microbiome to influence neural development, cognition, and behavior. There has also been evidence that the gut microbiota composition can be altered due to changes in behavior, and changing the microbiome can also cause depressive-like behaviors. Microbial colonies also excrete many different types of waste byproducts. Using different waste removal mechanisms, under normal circumstances the body effectively manages these byproducts with little or no trouble. Unfortunately, oversized and inappropriately large colonies, due to their increased numbers, excrete increased amounts of these byproducts. As the amount of microbial byproducts increases, the higher waste byproducts levels can overburden the body's waste removal mechanisms. A human’s
microbiome A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably wel ...
can change because of inflammatory processes, such as cell-mediated inflammation and host-mediated inflammation, or a ‘driver’ bacteria causing/aggravating inflammation. This change allows the microbial community to become more susceptible to pathogens. Once the pathogens are established successfully, they contribute to dysbiosis and produce genotoxins and other potential cancer-causing microbial metabolites. The evolution of pathogens is another possible effect of dysbiosis, contributing to a potential increase in cancer risk. The density of bacteria in the colon is high (about 1012 per ml.), and these bacteria are subject to dysbiosis. By contrast, the
small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...
has a relatively low density of bacteria (about 102 per ml.) so that dysbiosis is likely less of a problem. This difference may account for the greater than 10-fold higher incidence of cancer in the colon compared to the small intestine. The risk of Intestinal cancer is associated with a Western high fat diet that increases susceptibility to secondary bile acid induced dysbiosis. Exposure of the colon to an increased level of secondary bile acids resulting from dysbiosis can cause DNA damage, and such damage can cause carcinogenic mutations in colon cells. Gut dysbiosis can affect the cardiovascular system “via signaling molecules and bioactive metabolites. This could cause diseases through neuro-entero-endocrine hormones that can lead to heart failure and other conditions such as chronic kidney disease, hypertension, obesity, and diabetes.


Associated illnesses

Cross-regulation occurs between the host and the gut microbiota in healthy people, resulting in a homeostatic equilibrium of bacteria that keeps the gastrointestinal tract healthy and free of potentially pathogenic bacteria. There are three significant categories of dysbiosis: loss of beneficial organisms, excessive growth of potentially harmful microorganisms, and loss of overall microbial diversity. Disruptions in the microbiome can allow outside factors or even pathogenic members of the microbiome to take hold in the gut environment. Dysbiosis has been reported to be associated with illnesses, such as multiple chemical sensitivity, periodontal disease,
inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...
,
chronic fatigue syndrome Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling Chronic condition, chronic illness. People with ME/CFS experience profound fatigue that does not go away with rest, as well as sleep issues and problems with memory ...
,
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
,
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
,
bacterial vaginosis Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urina ...
, and colitis.


Inflammatory bowel disease

There is no single or well-understood microbial cause of
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...
, but three major pathogens have been associated with Crohn's disease: '' Mycobacterium avium paratuberculosis'' (MAP), adherent-invasive ''
Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'' (AIEC), and '' Clostridioides difficile''. The causal role, if any, these bacteria play has yet to be determined. Rather than the "one-microbe-one disease" hypothesis, some think that Crohn's is caused by an imbalance of commensal microflora associated with more complex interactions between the host and the entire intestinal microbiota.


Obesity

Obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
is a metabolic condition in which the body retains an unhealthy amount of fat. Similar to IBD, a specific microbiota appears to be linked to the development of obesity. There is a notable reduction in microbial diversity in obese individuals. Research in humans and animals shows an association of obesity with altered ratios between Bacteroidetes and Firmicutes; as Bacteriodetes decreases, Firmicutes increases. This ratio has been linked to body weight and fat accumulation, indicating that obese people have a higher disproportionate ratio of these bacteria.


Diabetes mellitus

Diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...
(DM) is a carbohydrate metabolism disorder characterized by insufficient insulin output or utilization, which is needed for the body to turn sugars and starches into energy. The prevalence of DM in the United States is about 29.1 million, with about 1.7 million new diagnoses annually. The two forms of diabetes are Type 1 and Type 2. Type 1 DM is also known as Insulin-Dependent Diabetes Mellitus (IDDM). Type 1 diabetes is an autoimmune condition that affects the beta cells in the pancreas, causing insulin production to be impaired. It is most often diagnosed in children and young adults. Type 2 diabetes mellitus, also known as Non-Insulin-Dependent Diabetes Mellitus (NIDDM), is a type of diabetes that affects adults and is characterized by insulin resistance, which occurs when tissue sensitivity insulin is reduced, causing the body to ignore the insulin released. Research has shown dysbiosis of the intestinal microbiota may contribute to both forms of diabetes. Dysbiosis related to type 1 DM is characterized by a decline in mucin-degrading bacteria, such as Bifidobacteria, Lactobacillus, and Prevotella, and an increase in Bacteroidetes and Clostridium.


Cancer

Sustained periods of dysbiosis lead to extended amounts of stress and inflammation in the gut microbiome, which can in turn promote the production of carcinogenic metabolites. Intestinal dysbiosis has been associated with colorectal cancer (CRC). According to the American Cancer Society, colorectal cancer is the third most common cancer and the second leading cause of cancer death in the United States. In CRC patients, a general dysbiosis pattern has been discovered, including a decrease in butyrate-producing bacteria and an increase in the proportion of several potentially pathogenic bacteria.


''Clostridioides difficile''

'' C. difficile'' is an opportunistic bacteria that commonly infects patients following a disruption in the microbiome, such as treatment with antibiotics. Infection can lead to several different symptoms including watery diarrhea, fever, loss of appetite, nausea, and abdominal pain. Severe or chronic infections of ''C. difficile'' can lead to inflammation of the colon, a condition known as colitis.


Periodontitis

Periodontitis is an oral infection that can damage the bones supporting teeth and lead to tooth loss. One of the major risk factors for periodontitis is the disruption of the oral microbiome such that there is an accumulation of pathogenic bacteria. Studies show that the oral microbiota changes as periodontitis progress, shifting from gram-positive aerobes to gram-negative anaerobes. Oral dysbiosis is likely to evolve, shifting the symbiotic host-microbe relationship to a pathogenic one. During this time, the host's oral health deteriorates, eventually leading to clinical disease.


Acne vulgaris

The use of minocycline in acne vulgaris has been associated with skin and gut dysbiosis.


Cardiovascular disease

Dysbiosis of intestinal microbiota may accelerate the progression of
cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
. Dietary habits, high stress, intestinal infections and use of antibiotics can cause an imbalance in the species and quantity of microorganisms in the adult intestine. Gut dysbiosis may lead to
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
and metabolic disorders that promote the development of cardiovascular disease.


Treatments


Antibiotics

Because of the complex interactions in the microbiome, not much data exists on the efficacy of using antibiotics to treat dysbiosis. However, the broad-spectrum antibiotic rifaximin has been shown to have a favorable response in several of the ailments associated with dysbiosis, including
irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...
. While most antibiotics alter the gut microbiota for the duration of the treatment, some cause long-lasting changes. However, repeated exposure to antibiotics can also cause the opposite of the intended effect and destabilize the gut microbiome, resulting in promoting “outgrowth of antibiotic-resistant pathogenic bacteria” (see antibiotic misuse) thus aggravating gut dysbiosis.


Fecal microbiota transplant (FMT)

Fecal Microbiota Transplantation (FMT) is an experimental treatment that has resolved 80–90 percent of dysbiosis-related infections caused by recurrent ''C. difficile'' infections that do not respond to antibiotics in randomized, controlled clinical trials. A patient's colon is transplanted during FMT with a fecal preparation from a carefully screened, healthy stool donor. FMT is thought to work by repopulating the patient's microbiome with various microorganisms that compete with ''C. difficile'' for space. FMTs use the same line of reasoning as probiotics; to recreate a healthy balance of microbiota in the microbiome by inserting beneficial microbes into the environment. FMT accomplishes this by taking a donation of fecal matter from a healthy individual, diluted, strained and introduced to a diseased patient. FMTs are currently used to treat patients with Clostridioides difficile infections, who have proved resistant to other therapies.; however, this is considered an investigational therapy at present with risks that have not been fully defined. FMT is also being investigated for use in psychiatric disorders. Because the process is not sterile and contaminations can pass from donor to patient, there is a push to isolate key microbiota and culture them independently.


Probiotics

The World Health Organization defines probiotics as "live microorganisms, which when administered in adequate amounts, confer a health benefit on the host". The benefit of using probiotics to treat dysbiosis related diseases lies in its ability to treat the underlying cause of said diseases. Some benefits include their ability to suppress inflammation in the microbiome and disrupt colonization by pathogens. Excessive use of antibiotics, IBD, obesity, diabetes, cardiovascular disease, and many more ailments are related to interruptions in the microbiome(dysbiosis), especially in the human gut. Probiotics can promote healthier microbial function by introducing or reintroducing helpful bacteria to strengthen the weaknesses presented in a dysbiotic microbiome. It is essential to recognize that such circumstances are beneficial bacteria that occur more frequently than harmful ones. Probiotics can be utilized in aiding existing conditions and preventing such diseases by instituting anti-inflammatory properties and improving immune cell function. The human gut contains a wide diversity of bacteria and can easily be disrupted through diet, medicinal usage, diseases, and many others. Probiotics have proven influential in returning the intestinal microbiota to homeostatic balance and improve intestinal health. Probiotics contain anti-inflammatory properties that assist in the prevention and treatment of intestinal diseases due to microbial dysbiosis. More research is needed to understand better the many benefits probiotics can offer for multiple forms of dysbiosis. Lactobacillus is the most researched single strain of probiotic bacteria. It is sold to consumers for gut health either as a single strain or part of a multi-strain formulation.


See also

* Human microbiome * List of bacterial vaginosis microbiota


Notes and references


External links


Intestinal dysbiosis
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